The aromatic hydrocarbon (Ah) receptor is an intracellular protein that binds and mediates the biological effects of the environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The liganded Ah receptor heterodimerizes with a second protein (known as Arnt) in activating CYP1A1 gene transcription in mouse hepatoma cells. The proposed studies involve: (1) analyses of the functional domains of the Ah receptor, (2) identification of additional protein partners for the receptor, and (3) characterization of receptor function in the absence of TCDD. The experiments utilize a variety of techniques in molecular biology, cellular biology, and genetics. The studies are designed to generate new insights into the mechanism of TCDD action; the findings may help in assessing the risk that dioxin poses to human health.